Maternal HIV infection influences the microbiome of HIV-uninfected infants

Abstract

More than 1 million HIV-exposed, uninfected infants are born annually to HIV-positive mothers worldwide. This growing population of infants experiences twice the mortality of HIV-unexposed infants. We found that although there were very few differences seen in the microbiomes of mothers with and without HIV infection, maternal HIV infection was associated with changes in the microbiome of HIV-exposed, uninfected infants. Furthermore, we observed that human breast milk oligosaccharides were associated with bacterial species in the infant microbiome. The disruption of the infant's microbiome associated with maternal HIV infection may contribute to the increased morbidity and mortality of HIV-exposed, uninfected infants.

Fig. 1. Microbiomes of 50 mother infant dyads

Overall, we found differences in the microbiomes based on the site of sample collection. (A) Principle coordinates analysis of unweighted UniFrac distances revealed that each sample type clustered into distinct groups. (B) α-diversity (Shannon index) was similar for all sample sites except for the vagina which was significantly less diverse than other sample sites (p=0.021). (C) Bacterial compositions across sample sites (mother: areolar skin, breast milk, vagina; infant: mouth, skin, stool) at the taxonomic level of family. (D) Heatmap representation of individual bacterial compositions at the family level. Families with an overall relative abundance of less than 0.5% are omitted for the sake of clarity.

Fig. 2. Minimal effects of HIV infection on maternal microbiomes

(A) Principle coordinates analysis of unweighted UniFrac distances based on mother’s HIV status at each sample site (areolar skin, breast milk, vagina). (B) α-diversity (Shannon index) at each sample site based on mother’s HIV status. (C) Bacterial compositions across sample sites at the taxonomic level of family. (D) Heatmap representation of individual bacterial compositions at the family level. Families with an overall relative abundance of less than 0.5% are omitted for the sake of clarity. (E) List of all taxa at any level or sample site that were significantly different based on mother’s HIV status using corrected p values (fdr_p values <0.1).

Fig. 3. Effects of maternal HIV infection on the infant microbiome

(A) Principle coordinates analysis of unweighted UniFrac distances based on mother’s HIV status at each infant sample site (mouth, skin, stool). (B) α-diversity (Shannon index) at each infant sample site based on mother’s HIV status. (C) Bacterial compositions across infant sample sites at the taxonomic level of family. (D) Heatmap representation of individual bacterial compositions at the family level. Families with an overall relative abundance of less than 0.5% are omitted for the sake of clarity. (E) List of all taxa at any family level or infant sample site that were significantly different based on mother’s HIV status using corrected p values (fdr_p values <0.1).

Fig. 4. Microbiome dysbiosis in HIV-exposed, uninfected infants

(A) Random forest classification scheme to identify taxa associated with HIV status. Bacterial taxa enriched in HIV-unexposed infants are represented on the left, with bacterial taxa enriched in HIV-exposed uninfected infants on the right. (B) Bayesian estimate of the proportion of microbes in the infant samples that came from the mother. (C) A relative maturity index was calculated for each experimental sample based on the relative stool microbiome age versus the age of the subject at collection. This was then plotted along with the normalized midline of the previously published reference cohort of healthy controls.

Fig. 5. Human breast milk oligosaccharide (HMO) composition and the infant stool microbiome

(A) The HMO composition of breast milk based on maternal HIV status. Unadjusted p values